**3. Pathobiology of** *Campylobacter* **infections**

#### **3.1 Incubation period**

The incubation period of *Campylobacter* ranges from 2 to 5 days in avian species. Birds can be infected by *Campylobacter* naturally, and experimental infection of *Campylobacter* can also be produced in birds but mostly the clinical signs are not visible. The appearance of clinical signs especially gastrointestinal signs is related to the age of the host. Chickens experimentally infected with *Campylobacter* on the first day, 12 hours post-hatching, resulted in the appearance of diarrhea while no clinical manifestation of campylobacteriosis was observed in 3-day-old chicks that were infected with 10<sup>9</sup> organisms [23]. In a day-old chick, a dose of as low as 2 cfu, has been established for *Campylobacter* colonization [24]. Chickens aged between 2 and 3 weeks of age, reared at commercial farms, have not been shown to be infected by *Campylobacter* infection and it may be associated with the presence of maternal antibodies [25, 26]. Flocks infected with *Campylobacter* specifically *C. jejuni* will shed the organism for at least 12 weeks of age [27]. The shedding may continue for 42 weeks in the breeder birds [28]. The incubation period of *Campylobacters* in humans is from 2 to 4 days but can range from 1 to 10 days [29].

#### **3.2 Clinical signs and pathological lesions**

Under natural conditions, clinical signs are not observed in poultry infected with *Campylobacter*. Clinical signs, including weight loss and diarrhea, have been reported in young birds that have been experimentally challenged with *Campylobacter* infection [30], and diarrhea may last for 7–14 days. The gastrointestinal tract was reported to be the site where minimal microscopic and pathological lesions were observed in experimentally infected birds [31]. Gross lesions observed in chicks infected by *Campylobacter* included mucus and fluid-filled distended jejunum [32] and petechial hemorrhages of the mucosa [23]. The microscopic

lesions include edema of mucosa and submucosa of the GIT, especially in the cecum [23] and *Campylobacter* may be found attached to the brush border of enterocytes [32]. In severe conditions, the intestinal lumen may be filled with erythrocytes and leukocytes due to mononuclear infiltration of the submucosa and villous atrophy [23].

Consumption of raw milk, non-chlorinated or contaminated surface water, and ingestion of raw or undercooked poultry or red meat are some of the ways that humans might contract *Campylobacter* infections. Close contact with sick pets in a household setting can also result in human *Campylobacter* infections [33]. *Shigella* and *Salmonella* infections can sometimes be difficult to distinguish clinically from *Campylobacter* infections [34]. The mechanisms of *Campylobacter* survival and infection are poorly known, but when it colonizes the ileum, jejunum, and colon, it can occasionally result in infection with or without symptoms. The transmission cycle of *Campylobacter* infections is shown in **Figure 1**.

Human gastroenteritis is frequently brought on by *Campylobacter*, however, the infection can also develop beyond the intestines. Two forms of *Campylobacter* infections exist, that is, gastrointestinal infection (GI) and extragastrointestinal infection (EI). Diarrhea is typically a symptom of gastroenteritis, an inflammation of the gastrointestinal tract that affects the small intestine and stomach. *Campylobacter* is one of the four major bacterial causes of gastrointestinal illnesses worldwide [35]. Moreover, it is a significant and frequent cause of children's diarrhea and traveler's diarrhea [36]. Reactive arthritis, Guillain-Barre syndrome (GBS) [37], bacteremia, septicemia, septic arthritis, endocarditis, neonatal sepsis, osteomyelitis, and meningitis are among the extragastrointestinal illnesses linked to *Campylobacter* infections [1]. Other extragastrointestinal post-infections linked to Campylobacter infections include severe neurological dysfunction, neurological abnormalities, and paralysis resembling polio in a rare number of patients [35].

**Figure 1.** *The transmission cycle of Campylobacter infections.*

#### **3.3 Pathogenesis of the** *Campylobacter* **infections**

The ability of *Campylobacter* to survive outside the gut is very low and it does not replicate outside the gut [38] and temperature ranging from 37 to 42°C is suitable for its growth. Thus, a chicken's body temperature (41–42°C) is suitable for the growth and survival of *Campylobacter* [39]. *Campylobacter* species gain entry into the body of the bird *via* the fecal-oral route and colonize the caecum, cloaca, and distal jejunum [40]. The most probable site for the colonization of *Campylobacter* are the crypts of the cloaca and cecum but it may be found in minute levels in the small intestine and gizzard. The colonization of *Campylobacter* in the intestine of birds is affected by various factors [41]. Colonization of intestinal epithelium is accomplished by chemotaxis with the help of chemoattractants, including mucin and L-Fucose [42]. Flagellum helps the organism in its movement in a viscous fluid and helps it in colonizing the intestinal mucosa. Different outer membrane proteins and LPS have been associated with adhesion and invasion. After colonizing the intestinal epithelium of the intestine, CLT (cholera-like-toxin) and cytotoxin result in tissue damage leading to inflammation followed by leakage of serosal fluid [38].
